The incidence and mortality of lung cancer continue to rise and attempts at "early" diagnosis to improve prognosis appear to have increased overall five year survivals to no more than 15-20%. We propose that the pathogenesis of lung cancer is a progressive pattern of bronchial epithelial atypias extending over a period of 20-30 years, with first squamous metaplasia followed, in turn, by mild, moderate and severe epithelial atypia and culminating in carcinoma. We believe that by periodic cytologic sputum examination, individuals with moderate to severe epithelial atypias who are at high risk for development of lung cancer can be identified and counseled regarding cessation of smoking, transferred to a less hazardous occupational exposure, and possibly treated with retinoids to prevent further progression of their bronchial atypias. To realize these objectives, we believe it imperative that definite objective morphometric criteria be established for the identification of the atypical bronchial epithelial cells in sputum. To accomplish this goal, we propose to use scanning microscope photometry coupled with various statistical cell image analysis techniques, as were developed in our previous NCI contract (N01 CP 65837), entitled "Markers for Evaluation of Pre-Neoplastic Lesions in the Respiratory Tract".